US9850236B2ActiveUtilityPatentIndex 71
Trifluoromethyl alcohols as modulators of RORγt
Est. expiryOct 30, 2034(~8.3 yrs left)· nominal 20-yr term from priority
Inventors:GOLDBERG STEVENVENKATESAN HARIHARANTANIS VIRGINIAKINZEL OLAFGEGE CHRISTIANSTEENECK CHRISTOPHKLEYMANN GERALDHOFFMANN THOMASFOURIE ANNE MXUE XIAOHUA
A61P 37/02A61P 43/00A61P 37/00A61P 3/10A61P 37/06A61P 3/00A61P 29/00A61P 11/06A61P 17/06A61P 19/00A61P 1/04A61P 1/12A61P 11/00A61P 17/00A61P 25/00A61P 11/02A61P 19/02A61K 31/4439A61K 31/426A61K 31/454A61K 45/06C07D 495/10A61K 31/4709A61K 31/541C07D 487/08A61K 31/427C07D 417/14C07D 277/56C07D 417/06
71
PatentIndex Score
2
Cited by
79
References
43
Claims
Abstract
The present invention comprises compounds of Formula I. wherein: X, A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , and R 3 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1. A compound of Formula I:
wherein
X is CH, CR 1 , or N;
A 1 is C (1-2) alkyl;
A 2 is cyclobutyl, or C (1-4) alkyl, wherein said C (1-4) alkyl is optionally substituted with OCH 3 or up to three fluorine atoms;
or A 1 and A 2 are taken together with their attached nitrogen to form a ring selected the group consisting of azetidinyl, piperidinyl, pyrrolidinyl,
wherein said ring is optionally substituted with up to three substituents independently selected from the group consisting of F, CF 3 , CH 3 , —CN, and CH 2 OH;
R 1 is Cl, C(CH 3 ) 3 , CH 2 CH 3 , OCF 3 , CF 3 , OCH(CH 3 ) 2 , CHF 2 , OCHF 2 , OCH 3 , F, CH 3 , or —CN;
R 2 is H, F, or Cl;
or R 1 and R 2 may be taken together with their attached phenyl to form a naphthalenyl, or quinolinyl group;
R 3 is CF 3 , or CH 2 CH 3 ;
A 3 is H
A 4 is H, C (1-5) alkyl,
wherein said C (1-5) alkyl is optionally substituted with one to two substituents independently selected from COOH, CONH 2 , —CN, and OH;
or A 3 and A 4 may be taken together with their attached nitrogen to make a ring selected from the group consisting of
and pharmaceutically acceptable salts thereof.
2. The compound of claim 1 wherein:
R 1 is Cl, C(CH 3 ) 3 , CH 2 CH 3 , OCF 3 , CF 3 , OCH(CH 3 ) 2 , CHF 2 , OCHF 2 , OCH 3 , F, or CH 3 ;
A 4 is H, C (1-5) alkyl,
wherein said C (1-5) alkyl is optionally substituted with one to two substituents independently selected from CONH 2 , —CN, and OH;
and pharmaceutically acceptable salts thereof.
3. The compound of claim 2 , of Formula II:
and pharmaceutically acceptable salts thereof.
4. The compound of claim 2 selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
5. The compound of claim 3 selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
6. The compound of claim 1 selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
7. A pharmaceutical composition, comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition made by mixing a compound of claim 1 and a pharmaceutically acceptable carrier.
9. A process for making a pharmaceutical composition comprising mixing a compound of claim 1 and a pharmaceutically acceptable carrier.
10. A method for treating or ameliorating a RORγt mediated inflammatory syndrome, disorder or disease selected from the group consisting of: inflammatory bowel diseases, rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disorder, psoriatic arthritis, ankylosing spondylitis, neutrophilic asthma, steroid resistant asthma, multiple sclerosis, and systemic lupus erythematosus, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .
11. The method of claim 10 , wherein the disease is psoriasis.
12. The method of claim 10 , wherein the disease is rheumatoid arthritis.
13. The method of claim 10 , wherein the inflammatory bowel disease is ulcerative colitis.
14. The method of claim 10 , wherein the inflammatory bowel disease is Crohn's disease.
15. The method of claim 10 , wherein the disease is multiple sclerosis.
16. The method of claim 10 , wherein the disease is neutrophilic asthma.
17. The method of claim 10 , wherein the disease is steroid resistant asthma.
18. The method of claim 10 , wherein the disease is psoriatic arthritis.
19. The method of claim 10 , wherein the disease is ankylosing spondylitis.
20. The method of claim 10 , wherein the disease is systemic lupus erythematosus.
21. The method of claim 10 , wherein the disease is chronic obstructive pulmonary disorder.
22. The compound of claim 5 selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
23. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
24. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
25. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
26. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
27. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
28. The compound of claim 22 that is:
and pharmaceutically acceptable salts thereof.
29. A pharmaceutical composition, comprising a compound of claim 22 and a pharmaceutically acceptable carrier.
30. A pharmaceutical composition made by mixing a compound of claim 22 and a pharmaceutically acceptable carrier.
31. A process for making a pharmaceutical composition comprising mixing a compound of claim 22 and a pharmaceutically acceptable carrier.
32. A method for treating or ameliorating a RORγt mediated inflammatory syndrome, disorder or disease selected from the group consisting of: inflammatory bowel diseases, rheumatoid arthritis, psoriasis, chronic obstructive pulmonary disorder, psoriatic arthritis, ankylosing spondylitis, neutrophilic asthma, steroid resistant asthma, multiple sclerosis, and systemic lupus erythematosus, comprising administering to a subject in need thereof an effective amount of a compound of claim 22 .
33. The method of claim 32 , wherein the disease is psoriasis.
34. The method of claim 32 , wherein the disease is rheumatoid arthritis.
35. The method of claim 32 , wherein the inflammatory bowel disease is ulcerative colitis.
36. The method of claim 32 , wherein the inflammatory bowel disease is Crohn's disease.
37. The method of claim 32 , wherein the disease is multiple sclerosis.
38. The method of claim 32 , wherein the disease is neutrophilic asthma.
39. The method of claim 32 , wherein the disease is steroid resistant asthma.
40. The method of claim 32 , wherein the disease is psoriatic arthritis.
41. The method of claim 32 , wherein the disease is ankylosing spondylitis.
42. The method of claim 32 , wherein the disease is systemic lupus erythematosus.
43. The method of claim 32 , wherein the disease is chronic obstructive pulmonary disorder.Cited by (0)
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